Fig. 4

Unique switch orientations of Rab11-SH3BP5 compared to previously solved Rab-GEF structures. a Structures of nucleotide-bound Rab11 are compared to the GEF bound structures of Rab11-SH3BP5 (dotted box), Rab35-DENND1B⁴³, Ypt7-Mon1-Ccz1⁴⁴, Sec4p-Sec2p⁴⁷, Ypt1p-TRAPPI⁵², Rab21-Rabex-5⁷⁰, and Rab1b-DrrA⁵⁶. The Rab GTPases are aligned to each other, with the GEF domain shown as a transparent surface. Switch I and II are colored according to Fig. 2, and the residues corresponding to F36 residue and I44 in Rab11 are labeled on all structures (the residue corresponding to F36 is disordered in the Ypt1p-TRAPPI complex, and in the Rab21-Rabex-5 structures). b Alignment of the Switch I of Rab11 to a selection of closely related Rab isoforms and all previously solved Rab-GEF structures (PDB codes indicated). Switch I residues shown as sticks are highlighted by arrows. c Alignment of the coiled coil GEF domains of SH3BP5 and Sec2P (Rabin8)⁴⁷. This reveals a completely orthogonal binding interface, with the two GEF coiled coils binding to their cognate Rab in a perpendicular orientation, revealing independent evolution of coiled coils as Rab-GEFs